All publications herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. The following description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
Vascular bypass grafting is the mainstay of revascularization for ischemic heart disease and peripheral vascular disease, and in the US alone 1.4 million arterial bypass operations are performed annually. However, 30% of patients who require arterial bypass procedures do not have saphenous veins suitable for use, because of previous harvest for bypass surgery, varicose degeneration, or inadequate diameter or length (McKee, J. A., Banik, S. S., Boyer, M. J., Hamad, N. M., Lawson, J. H., Niklason, L. E., and Counter, C. M. 2003 EMBO Rep 4:633-638). To overcome this limitation, synthetic materials are frequently used for treatment of peripheral vascular disease. However, they are limited to high flow/low resistance conditions (Whittemore, A. D., Kent, K. C., Donaldson, M. C., Couch, N. P., and Mannick, J. A. 1989 J Vasc Surg 10:299-305; Faries, P. L., Logerfo, F. W., Arora, S., Hook, S., Pulling, M. C., Akbari, C. M., Campbell, D. R., and Pomposelli, F. B., Jr. 2000 J Vasc Surg 32:1080-1090) because of poor elasticity (Gozna, E. R., Mason, W. F., Marble, A. E., Winter, D. A., and Dolan, F. G. 1974 Can J Surg 17:176-179 passim), low compliance, and thrombogenicity of synthetic surfaces (Greisler, H. P. 1990 Ann Vasc Surg 4:98-103). The artificial materials, when used to bypass arteries of this size, have thrombosis rates greater than 40% after 6 months (Sayers, R. D., Raptis, S., Berce, M., and Miller, J. H. 1998 Br J Surg 85:934-938). Despite attempts to improve synthetic polymer grafts, the thrombosis rate has remained high. In addition, foreign body reaction to the synthetic material further confounds the utility of the implants. Recent evidence demonstrates that stem cells can contribute to the regeneration of fibrous tissue in the area of injury. The inventors offer evidence that the mouse peritoneum contains a significant number of stem cells, similar to the level found in bone marrow, which could contribute to formation of fibrous tissue.
A stem cell is a cell type that has a unique capacity to renew itself and give rise to specialized or differentiated cells. Although most cells of the body are committed to conduct a specific function, a stem cell is uncommitted, until it receives a signal to develop into a specialized cell type. What makes the stem cells unique is their proliferative capacity, combined with their ability to become specialized. Somatic stem cells are present in the adult organism. Pluripotency tests have shown that whereas the embryonic or blastocyst-derived stem cells can give rise to all cells in the organism, including the germ cells, somatic stem cells have a more limited repertoire in descendent cell types.
All blood cells that circulate in the peripheral blood are derived from primitive mesenchymal cells referred to as hematopoietic stem cells. In the adult, most of these cells are generally thought to be located in the bone marrow. Hematopoietic stem cells are self regenerating, and also pluripotent in that they differentiate into several lineages, including lymphoid, myeloid and erythroid lineages. It is believed that exposure to growth factors induces a stem cell to be dedicated to differentiate into a specific lineage.
Isolation of progenitor and/or stem cells from the peritoneal cavity has never been described. The identification of the peritoneal cavity as a new source of stem cells with attributes of hematopoietic and embryonic stem cells allows for further discovery of growth factors associated with self-regeneration, as well as growth factors associated with the early steps of dedication of the stem cell to a particular lineage, the prevention of such dedication, and the negative control of stem cell proliferation. The discovery of the peritoneal cavity as a source of stem cells can also be extremely useful as a substitute for bone marrow transplantation, as well as in transplantation of other organs currently performed in association with transplantation of bone marrow. Furthermore, stem cells are important targets for gene therapy, where the inserted genes promote the health of the individual into whom the stem cells are transplanted. Identification of the peritoneal cavity as a new source of stem cells thus provides additional means of isolating cells useful in gene therapy. Isolation of novel hematopoietic stem cell, or a novel intermediate in hematopoiesis, also provides new avenues for treatment of lymphomas and leukemias, as well as other neoplastic conditions. Finally, model systems to isolate and test stem cells and hematopoiesis also provide a means for testing agents that affect stem cells. Thus, there exists a need in the art for identification of new sources of hematopoietic embryonic stem cells.